itochondrion. There are two Alas isoenzymes: one (Alas1) is ubiquitously expressed, while the other (Alas2) is only expressed in erythroid cells. Transported to the cytosol, two ALAs are combined by delta-aminolevulinate dehydratase (Alad) to generate porphobilinogen (PBG).  Four PBG molecules are condensed by hydroxymethylbilane (or porphobilinogen) synthase (Hmbs) to form the linear tetrapyrrole hydroxymethylbilane, which is then cyclized by uroporphyrinogen III synthase (Uros; aka porphobilinogen deaminase) to form uroporphyrinogen III. Uroporphyrinogen decarboxylase (Urod) subsequently decarboxylates all four acetate groups of uroporphyrinogen III to form the methyl groups of coproporphyrinogen III. As coproporphyrinogen III is being transported back into the mitochondrion, coproporphyrinogen oxidase (Cpox) decarboxylates two of its propionate side chains to form the vinyl groups of protoporphyrinogen IX. Protoporphyrinogen oxidase (Ppox) then oxidizes the methylene groups connecting the pyrrole rings to form the methenyl linkages of protoporphyrin IX. In the final reaction of the heme biosynthetic pathway, ferrochetalase (Fech) , inserts ferrous iron into protoporphyrin IX to generate heme. Heme is synthesized mainly in erythroid cells, with the remainder generated in the liver. In the latter location, heme regulates its own synthesis by feedback inhibition of the pathway's first enzyme, Alas. In erythroid cells, heme synthesis is regulated by iron availability and shuts down as the cells mature. Alterations of the pathway due to mutations in its enzymes are associated with a number of diseases, most notably porphyrias.To see the Ontology Report for annotations GViewer and download click here
[Click here to see the ontology report for associated GO term - GO:0006695 and entry at Reactome - REACT_9465.1]...(less)